Human monoclonal antibodies (HMA) may not only demonstrate which antigens are immunogenic in the host, but also may be useful for prolonged MA therapy when murine antibodies have elicited antiglobulin responses to the Fc region. We have demonstrated that stable, HMA-secreting clones may be produced with various human myeloma cell lines, but that the efficiency of this process is low. We have also demonstrated that HMA-secreting hybrids between human lymphocytes and mouse myelomas may be grown in the peritoneal cavities of nude mice to produce highly concentrated human immunoglobulins. Although we developed an in vitro model system to stimulate human lymphocytes prior to cell fusion for HMA production utilizing tetanus toxoid as a model antigen, this has not as yet been successfully applied to tumor antigens. Current work is focused on isolating B-cells with surface membrane antibody directed at the 250 Kd melanoma associated antigen and then expanding these lymphocytes in B-cell growth factor (BCGF) prior to fusion.